1. Effect of luteolin on the gene level expression of apoptosis-associated speck-like protein containing a caspase recruitment domain of NLRP3 inflammasome and NF-κB in rats subjected to experimental pancreatitis - influence of HSP70
- Author
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Arumugam Geetha and Sadanandan Rajapriya
- Subjects
Male ,medicine.medical_specialty ,Normal diet ,Physiology ,Inflammasomes ,Apoptosis ,medicine.disease_cause ,Pyrin domain ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Downregulation and upregulation ,Internal medicine ,Drug Discovery ,NLR Family, Pyrin Domain-Containing 3 Protein ,medicine ,Animals ,HSP70 Heat-Shock Proteins ,Rats, Wistar ,Luteolin ,030304 developmental biology ,Pharmacology ,0303 health sciences ,biology ,Ethanol ,Glutathione Disulfide ,Body Weight ,Caspase 1 ,NF-kappa B ,Inflammasome ,General Medicine ,Rats ,Endocrinology ,chemistry ,Caspase Activation and Recruitment Domain ,Pancreatitis ,030220 oncology & carcinogenesis ,Myeloperoxidase ,biology.protein ,Oxidative stress ,Ceruletide ,medicine.drug - Abstract
Objectives Nod-like receptor pyrin domain containing 3 (NLRP3) is one of the well characterized inflammasome that controls the maturation of pro-inflammatory cytokines and thereby the inflammation in pancreas which could be a promising target for anti-inflammatory drugs. The present study is aimed to explore whether luteolin can target the NLRP3 inflammasome and modulate its activity through the signaling protein, HSP70 in the ethanol-cerulein model of experimental pancreatitis. Methods Male albino Wistar rats were divided into four groups. Groups 1 and 2 rats received normal diet. Groups 3 and 4 rats received isocalorically adjusted diet containing ethanol for 5 weeks and cerulein (20 μg/kg body weight i.p., thrice weekly for the last 3 weeks of the experimental period). Additionally, group 2 and 4 rats received 2 mg/kg body weight of luteolin orally from third week. Results Luteolin co-administration decreased the serum levels of HSP70, oxidative stress markers, myeloperoxidase, GSH/GSSG and GST with concomitant downregulation in the mRNA expression of HSP70, caspase-1, ASC-NLRP3 and NF-κB. Spearman’s rank correlation test showed that serum HSP70 has positive correlation with the expression of ASC-NLRP3, caspase-1, NF-κB and 4-hydroxynonenal and negative correlation with GSH:GSSG ratio. Conclusions The modulating effect of luteolin on the expression of HSP70, NF-κB and thereby on ASC-NLRP3 complex may be claimed for its pancreato-protective activity.
- Published
- 2020